PhD Scientific Days 2026

Molecular Medicine 4.

The Ephrin/Eph Landscape of Colorectal Cancer

Name of the presenter

Carmi, Idan

Institute/workplace of the presenter

Semmelweis University, Institute of Genetics, Cell- and Immunobiology

Authors

Dr. Idan Carmi¹, Dr. Zoltán Wiener¹
1: Semmelweis University, Institute of Genetics, Cell- and Immunobiology

Text of the abstract

Colorectal cancer (CRC) is a leading cause of cancer-related mortality in Hungary. Its progression is strongly influenced by stromal cells and receptor-mediated signaling pathways. Eph receptors and their ephrin (EFN) ligands constitute the largest family of receptor tyrosine kinases and are key regulators of cell positioning, adhesion, and invasion across various tumor types. However, their expression patterns in CRC remain insufficiently characterized.
Aims:
To comprehensively characterize Eph and EFN expression by integrating database analyses with studies on CRC patient-derived organoids (PDOs).
Methods:
Gene expression was analyzed using RT-qPCR, confocal microscopy, and flow cytometry in CRC PDOs. Publicly available datasets, including the Protein Atlas and single-cell RNA sequencing (scRNA-seq) data, were also evaluated. Statistical analyses were performed on all datasets.
Results:
scRNA-seq analysis revealed the presence and intratumoral heterogeneity of EFNA1, EFNA3, EFNA4, EFNB1, EFNB2, EphA2, EphA4, EphB2, EphB3, and EphB4 in patient samples. These findings were consistent with RNA and protein expression data from the Protein Atlas. Screening of PDO lines demonstrated high RNA expression levels of these Eph/EFNs. In contrast, EFNA5, EphA4, and EphA5 transcripts were predominantly associated with cancer-associated fibroblasts. Notably, no major transcriptional differences in Eph receptor or EFN expression were observed between PDOs cultured in collagen I, an extracellular matrix component enriched in CRC, and those grown in laminin-rich Matrigel. Consistent with these results, EphA2 and EphB4 protein expression was confirmed in both PDOs and CRC tissue sections. Pharmacological inhibition targeting EphA2 and EphB4 resulted in reduced tumor cell survival in PDOs.
Conclusion:
Eph receptors and EFNs are broadly expressed in CRC, displaying patterns distinct from those in stromal fibroblasts. Their heterogeneous expression suggests that specific tumor cell subpopulations may rely on distinct Eph/EFN signaling pathways, which could serve as potential specific therapeutic targets.
Funding: K137554, 2024-1.2.3-HU-RIZONT-2024-00003 (National Research, Development and Innovation Office, Hungary), TKP2021-EGA-24 (Ministry of Innovation and Technology of Hungary). IC is supported by Pre-Doctoral funding. Ethical permission: TUKEB 2015, 51323-4/2015/EKU.